Immune dysfunction is commonly associated with several neurological and mental disorders. Although the mechanisms by which peripheral immunity may influence neuronal function are largely unknown, recent findings implicate meningeal immunity influencing behaviour, such as spatial learning and memory. Here we show that meningeal immunity is also critical for social behaviour; mice deficient in adaptive immunity exhibit social deficits and hyper-connectivity of fronto-cortical brain regions. Associations between rodent transcriptomes from brain and cellular transcriptomes in response to T-cell-derived cytokines suggest a strong interaction between social behaviour and interferon-γ (IFN-γ)-driven responses. Concordantly, we demonstrate that inhibitory neurons respond to IFN-γ and increase GABAergic (γ-aminobutyric-acid) currents in projection neurons, suggesting that IFN-γ is a molecular link between meningeal immunity and neural circuits recruited for social behaviour. Meta-analysis of the transcriptomes of a range of organisms reveals that rodents, fish, and flies elevate IFN-γ/JAK-STAT-dependent gene signatures in a social context, suggesting that the IFN-γ signalling pathway could mediate a co-evolutionary link between social/aggregation behaviour and an efficient anti-pathogen response. This study implicates adaptive immune dysfunction, in particular IFN-γ, in disorders characterized by social dysfunction and suggests a co-evolutionary link between social behaviour and an anti-pathogen immune response driven by IFN-γ signalling.
Showing posts with label Adaptive immune system. Show all posts
Showing posts with label Adaptive immune system. Show all posts
Characterization of salivary proteins of schizophrenic and bipolar disorder patients by top-down proteomics.
The analysis of whole saliva of 32 subjects with diagnosis of
schizophrenia (SZ), 17 with diagnosis of bipolar disorder (BD), and 31
healthy subjects divided in non smokers (HN; n=19) and smokers (HS;
n=12) using an HPLC-ESI-MS top-down platform is reported in this study.
Both SZ and BD revealed more than 10 fold mean increase of α-defensins
1-4, S100A12, cystatin A and S-derivatives of cystatin B levels with
respect to the HN and HS control groups. No differences of protein
levels were observed between SZ and BD groups and between HN and HS
groups. Moreover, the correlations coefficients among the different
proteins were significantly better in BD group than in SZ group.
study on whole saliva confirms a shizophrenia-associated dysregulation
of immune pathway of peripheral white blood cells and suggests that the
dysregulation of BD group could involve the activation of more specific
cell type than those of SZ group.
schizophrenia (SZ), 17 with diagnosis of bipolar disorder (BD), and 31
healthy subjects divided in non smokers (HN; n=19) and smokers (HS;
n=12) using an HPLC-ESI-MS top-down platform is reported in this study.
Both SZ and BD revealed more than 10 fold mean increase of α-defensins
1-4, S100A12, cystatin A and S-derivatives of cystatin B levels with
respect to the HN and HS control groups. No differences of protein
levels were observed between SZ and BD groups and between HN and HS
groups. Moreover, the correlations coefficients among the different
proteins were significantly better in BD group than in SZ group.
SIGNIFICANCE:
Thisstudy on whole saliva confirms a shizophrenia-associated dysregulation
of immune pathway of peripheral white blood cells and suggests that the
dysregulation of BD group could involve the activation of more specific
cell type than those of SZ group.
Activating killer-cell immunoglobulin-like receptors (KIR) and their cognate HLA ligands are significantly increased in autism.
Killer-cell immunoglobulin-like receptor (KIR) proteins are expressed on natural killer (NK) cells and appear important in innate and adaptive immunity. There are about 14 KIR genes on chromosome 19q13.4, composed of those that inhibit and those that activate NK cell killing. Haplotypes have different combinations of these genes meaning that not all genes are present in a subject. There are two main classes of cognate human leukocyte antigen (HLA) ligands (HLA-Bw4 and HLA-C1/C2) that bind to the inhibitory/activating receptors. As a general rule, the inhibitory state is maintained except when virally infected or tumor cells are encountered; however, both increased activation and inhibition states have been associated with susceptibility and protection against numerous disease states including cancer, arthritis, and psoriasis. Utilizing DNA from 158 Caucasian subjects with autism and 176 KIR control subjects we show for the first time a highly significant increase in four activating KIR genes (2DS5, 3DS1, 2DS1 and 2DS4) as measured by chi square values and odds ratios. In addition, our data suggests a highly significant increase in the activating KIR gene 2DS1 and its cognate HLA-C2 ligand (2DS1+C2; p=0.00003 [Odds ratio=2.87]). This information ties together two major immune gene complexes, the human leukocyte complex and the leukocyte receptor complex, and may partially explain immune abnormalities observed in many subjects with autism.
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